Study Explores Elevated Rates of Wet AMD Based on Medication Use, Genetics

WARS1, also called Tryptophanyl-tRNA synthetase 1, is a gene that encodes an essential enzyme for protein synthesis, as well as helping fight infections. Photo: Carolyn Majcher, OD. Click image to enlarge. Specific drugs were linked to higher reporting rates of neovascular age-related macular degeneration and six genes were found to be potential molecular mediators in a recent study published in Eye.Researchers analyzed 38.1 million adverse event reports spanning 20 years from the FDA Adverse Event Reporting System (FAERS). Among these, 2,509 reports mentioned wet AMD. The researchers divided the cohort between patients with wet AMD and those without it; Patients in the wet AMD group were 53.5% female and 34.4% were between 65 and 85 years old.Using multiple signal-detection methods and adjusted logistic regression analyses, the researchers then identified five drugs associated with significantly increased reporting risk for neovascular AMD: apixaban, carbamazepine, latanoprost, rituximab and semaglutide. The researchers noted that these associations remained significant after adjustment “for demographic and reporting confounders (age, gender, weight, reporter type, country and year).”Eye doctors will naturally question the inclusion of glaucoma mainstay latanoprost in this list, and the researchers themselves caution that “its association requires careful interpretation,” as it’s unlikely that any significant quantity would reach the RPE/choroid complex. “The signal may represent a true, albeit small, pharmacological effect or it may reflect confounding by indication or detection bias, where patients with glaucoma undergo more frequent ophthalmic surveillance,” they wrote. “Future studies should investigate whether this is a class effect of prostaglandin analogs by analyzing signals for other drugs such as travoprost or bimatoprost.”To investigate potential underlying genetic factors, the authors compiled 2,232 drug targets from other databases and explained in the paper that they combined the Mendelian randomization results from cohorts in each database used “to further investigate genetic associations.” They identified six genes—IGFBP6, MAPKAPK2, NFKB1, RGMA, RNASE1 and WARS1—as significantly associated with the risk of neovascular AMD. WARS1 showed the strongest support, with evidence suggesting a shared genetic signal between WARS1 expression and wet AMD.The authors then analyzed publicly available single-cell RNA sequencing datasets of retinal tissue, peripheral blood and blood outgrowth endothelial cells, all from patients who had wet AMD. Most genes were highly expressed in vascular remodeling endothelial cells, while “WARS1 expression was highly specific to CD16+ monocytes.”However, the authors cautioned that the findings were limited by the study’s “observational and exploratory” design. They concluded that the study could provide potential candidate targets for future clinical and experimental investigation.Click here for the journal source. Sun H, Bu f, Xiu X, Yan J, Huang T. Uncovering drug-associated risk signals for neovascular age-related macular degeneration: an integrative pharmacovigilance and proteogenomic study. Eye. June 1, 2026. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.